DESCRIPTION: The broad, long-term objective is to reduce morbidity and mortality caused by tumors occurring in the HNPCC syndrome. The first task is to define the natural history of HNPCC (e.g. age-dependent risk, spectrum of affected organs, clinical behavior) and the effect of predictive testing on clinical screening and preventive measures. his can be done by determining who is a carrier and who is not among as many as 288 affected and 1169 unaffected at-risk members of 81 previously diagnosed HNPCC families. The frequency of HNPCC will be determined by studying one-fourth of all colorectal carcinomas and adenomas removed in Finland. These will be screened for the replication error (RER) phenomenon that is indicative of, but not specific for, HNPCC. Individuals with RER-positive tumors will be screened for HNPCC mutations. This study will comprise some 2500 individuals annually. As there are almost no established procedures for the handling of data regarding individual susceptibility to a common, adult-onset cancer, the ethical and social aspects of this experiment in predictive testing will be researched by means of repeated individual counseling and evaluation, as well as by attempting to inform the medical profession, to educate the public, and to provide expertise to lawmakers.